DESCRIPTION: PP14 is an anti-inflammatory cytokine secreted by cells of the reproductive tract. Dr. Tykocinski has cloned a unique molecular form of PP14 produced in megakaryocytes and platelets and has developed both prokaryotic and eukaryotic expression systems for PP14. He proposes (1) molecular studies of human hematopoietic PP14 and its hydrophobic ligands and receptors; (2) further characterization of human hematopoietic PP14 and its immunosuppressive functions in in vitro systems; (3) studies of hematopoietic PP14 in platelets and its potential immunopathological consequences; (4) assessment of in vivo functions of PP14 in animal model systems, after prior cloning of respective animal PP14 homologues. Two central hypotheses will be tested: (1) PP14 and, in particular, human hematopoietic PP14 has immunotherapeutic potential as an anti-inflammatory cytokine for the treatment of inflammatory disorders; (2) PP14 from platelets is immunopathogenic in certain clinical settings.